In recent years, dementia has become a major medical problem worldwide. Dementia is a disease accompanied by various kinds of symptoms centering around learning and memory disorders and impaired judgment, and the symptoms and progress thereof vary depending on the diseases causing them. However, all cases are common in that the quality of life of patients is markedly impaired. Given the fact that caregivers including the patients' families are forced to offer a large amount of labor, dementia can be said a very serious problem at the social level. Since the increasing population of elderly citizens resulting from the increasing life span is related to the increase of dementia patients, the number of dementia patients is predicted to further increase in years ahead in Japan. In addition, there are many people suffering from aging-related cognitive impairment which is not classified as dementia.
As for dementia patients, various etiologies have been reported. Reported in Alzheimer-type dementia, Lewy body dementia and the like is a decrease in the intracerebral acetylcholine concentration. Use of an acetylcholine degrading enzyme inhibitor based on this fact is the most successful method to the present for the treatment of dementia, particularly Alzheimer-type dementia. In Japan, various kinds of acetylcholine degrading enzyme inhibitors have heretofore been developed, including already commercially available donepezil hydrochloride (trade name Aricept). However, such medicaments do not fundamentally treat dementia but show an effect of delaying the progression of symptoms. As for donepezil hydrochloride, moreover, the problem of side effects such as the risk of developing acute renal failure, rhabdomyolysis and the like has been reported. For these reasons, the development of a drug for improving dementia, which is safer and shows high effect, has been desired.
The present inventors found 8-(2-(2-pentyl-cyclopropylmethyl)-cyclopropyl)-octanoic acid (DCP-LA) as a compound having a long-term enhancing action on a synaptic transmission efficiency, which enables delay of metabolism in the body and intracerebral, stable physiological activity in the body, and can induce synaptic transmission long-term enhancing phenomenon (LTP, long-term potentiation) involved in learning and memory (patent document 1). LTP is considered to be involved in the onset of, for example, various nerve and mental diseases such as Alzheimer's disease and the like. Therefore, a substance that induces LTP expression has a possibility of becoming a therapeutic or prophylactic drug for such nerve and mental diseases including dementia.
Several reports are also available regarding DCP-LA. For example, there have been reported that DCP-LA selectively and directly activates PKC-ε (non-patent document 1), DCP-LA improves cognitive dysfunction of senescence-accelerated mouse (non-patent document 2), DCP-LA increases release of γ aminobutyric acid from hippocampus nerve cells (non-patent document 3), DCP-LA improves cognitive dysfunction of amyloid β peptide- or scopolamine-treated rat (non-patent document 4), and DCP-LA promotes hippocampus synaptic transmission by using, as a target, an α7 nicotinic acetylcholine receptor that expresses at the glutamatergic presynaptic terminal (non-patent document 5). In recent years, moreover, it has been reported that DCP-LA has an action to suppress nerve cell death induced by oxidative stress (patent document 2).